| ○種別 (必須): | □ | 学術論文 (審査論文)
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| ○言語 (必須): | □ | 英語
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| ○カテゴリ (推奨): |
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| ○学究種別 (推奨): |
| ○組織 (推奨): |
| ○著者 (必須): | 1. | 谷口 達哉
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| 2. | 岸 和弘
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| 3. | 中川 忠彦
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| 4. | (英) Tanaka Hironori (日) (読)
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| 5. | 田中 貴大
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| 6. | 友成 哲
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| 7. | 岡本 耕一 ([徳島大学.病院.診療科.内科.消化器内科])
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| 8. | 曽我部 正弘 ([徳島大学.キャンパスライフ健康支援センター])
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| 9. | 宮本 弘志 ([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.消化器内科学]/[徳島大学.病院.診療科.内科.消化器内科])
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| 10. | 岡久 稔也 ([徳島大学.大学院医歯薬学研究部.医学域.連携研究部門(医学域).寄附講座系(医学域).地域総合医療学]/[徳島大学.病院.診療科.内科.消化器内科])
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| 11. | 六車 直樹
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| 12. | (英) Kajimoto Mayumi (日) (読)
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| 13. | 佐川 幾子 ([徳島大学.大学院医歯薬学研究部.医学域.総合研究支援センター])
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| 14. | 高山 哲治 ([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.消化器内科学])
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| ○題名 (必須): | □ | (英) Poly-(ADP-Ribose) Polymerase-1 Promotes Prothrombin Gene Transcription and Produces Des-Gamma-Carboxy Prothrombin in Hepatocellular Carcinoma. (日)
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| ○要約 (任意): | □ | (英) Although des-gamma-carboxy prothrombin (DCP) is a well-known tumor marker for hepatocellular carcinoma (HCC), the mechanism of DCP production is unclear. This study aimed to investigate the mechanism how DCP is produced in HCC cells. Levels of mRNA and DCP were analyzed by real-time polymerase chain reaction and electro-chemiluminescence immunoassay respectively. Secreted alkaline phosphatase (SEAP) expression vectors including deletion mutants of the prothrombin gene promoter were constructed for reporter gene assay. The transcription factors bound to DNA fragments were analyzed by mass spectrometry. An electrophoretic mobility shift assay (EMSA) was performed using a biotin end-labeled DNA. The prothrombin mRNA levels in all 5 DCP producing cell lines were appreciably high. However, those in 2 DCP non-producing cell lines were below detectable levels. A SEAP vector with -2985 to +27 showed a very high transcription activity in DCP-producing Huh-1 cells. However, transcription abruptly decreased when the vector with -2955 to +27 was transfected, and then remained at the similar levels with larger deletion mutants, indicating the existence of a cis-element at -2985 to -2955 (31-bp). Mass spectrometry analysis identified the protein that bound to the 31-bp DNA as poly-(ADP-ribose) polymerase-1 (PARP-1). Knockdown of the PARP-1 gene by small interfering RNA in Huh-1 cells induced marked inhibition of prothrombin gene transcription. The EMSA clearly showed that PARP-1 specifically binds to the 31-bp DNA fragment in the prothrombin gene promoter. Our data suggest that PARP-1 activates prothrombin gene transcription and that the excessive prothrombin gene transcription induces DCP production in DCP-producing HCC cells. (日)
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| ○キーワード (推奨): |
| ○発行所 (推奨): |
| ○誌名 (必須): | □ | Digestion ([Karger])
(pISSN: 0012-2823, eISSN: 1421-9867)
| ○ISSN (任意): | □ | 1421-9867
ISSN: 0012-2823
(pISSN: 0012-2823, eISSN: 1421-9867) Title: DigestionTitle(ISO): DigestionPublisher: S. Karger AG (NLM Catalog)
(Scopus)
(CrossRef)
(Scopus information is found. [need login]) | [継承] |
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| ○巻 (必須): | □ | 95
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| ○号 (必須): | □ | 3
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| ○頁 (必須): | □ | 242 251
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| ○都市 (任意): |
| ○年月日 (必須): | □ | 西暦 2017年 4月 7日 (平成 29年 4月 7日)
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| ○URL (任意): |
| ○DOI (任意): | □ | 10.1159/000470837 (→Scopusで検索)
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| ○PMID (任意): | □ | 28384634 (→Scopusで検索)
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| ○備考 (任意): | 1. | (英) Article.ELocationID: 10.1159/000470837 (日)
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| 2. | (英) Article.PublicationTypeList.PublicationType: Journal Article (日)
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| 3. | (英) KeywordList.Keyword: Biomarkers (日)
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| 4. | (英) KeywordList.Keyword: Des-gamma-carboxy prothrombin (日)
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| 5. | (英) KeywordList.Keyword: Hepatocellular carcinoma (日)
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| 6. | (英) KeywordList.Keyword: Poly-(ADP-ribose) polymerase-1 (日)
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| 7. | (英) KeywordList.Keyword: Prothrombin (日)
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